Alzheimer's disease (AD) is a progressive and devastating neurodegenerative disorder of the elderly that is highlighted by a dramatic reduction of memory and cognition and linked to loss of neurons and synapses (Selkoe (2002) Science 298, 789-791). Additional key pathological features include the deposition of amyloid beta (Aβ), especially the 42-amino acid peptide (Aβ42), within neurons, amyloid plaques and in the walls of brain blood vessels, as well as the appearance of neurofibrillary tangles, glial activation and widespread inflammation (Schwab et al. (2008) J Alzheimers Dis 13, 359-369; Thal et al. (2008) Acta Neuropathol 115, 599-609; Weisman et al. (2006) Vitam Horm 74, 505-530). Aβ42 deposition within neurons is initiated early in the course of the disease, precedes amyloid plaque and tangle formation, and temporally and spatially coincides with loss of synapses in human AD and transgenic mouse brains (D'Andrea et al. (2001) Histopathology 38, 120-134; Nagele et al. (2002) Neuroscience 110, 199-211; Gouras et al. (2000) Am J Pathol 156, 15-20).
Studies have reported the presence of immunoglobulin (Ig)-immunopositive neurons in histological sections of post-mortem AD brains, which were only rarely observed in comparable brain regions of non-demented, age-matched controls (Stein et al. (2002) J Neuropathol Exp Neurol 61, 1100-1108; Bouras et al. (2005) Brain Res Brain Res Rev 48, 477-487; D'Andrea (2003) Brain Res 982, 19-30). The presence of specific brain-reactive autoantibodies in the serum of AD patients has also been reported. (Bouras et al. (2005) Brain Res Brain Res Rev 48, 477-487; Kulmala et al. (1987) Exp Aging Res 13, 67-72; Mecocci et al. (1993) Biol Psychiatry 34, 380-385; Mecocci et al. (1995) J Neuroimmunol 57, 165-170; Weksler et al. (2002) Exp Gerontol 37, 971-979).